The structure and function of the enteric nervous system will be investigated by electrophysiological and pharmacological techniques. Intracellular and extracellular recordings will be made from single neurons within the ganglia of the myenteric plexus of the guinea-pig ileum. Substances will be applied to neurons in vitro by perfusion and by microelectrophoresis. Putative neurotransmitters within the myenteric plexus will be studied. These include several neuropeptides (substance P, enkephalin, vasoactive intestinal polypeptide, somatostatin and neurotensin) as well as indoleamines. Their actions, ionic mechanisms and reversal potentials, will be compared with those of substances which mediate synaptic potentials. Recordings will be made from myenteric neurons in vivo in order to ascertain the normal firing patterns of single cells in the wall of the intestine. These studies will permit the extrapolation of previous findings to the intact animal, or indicate ways in which the in vitro preparations are inadequate. The results are expected to be of general significance in establishing or refuting a role for neuropeptides as neurotransmitters or neuromodulators, and of specific significance in elucidating the way in which myenteric neurons control gastrointestinal motility.